Synthetic lipopeptide vaccines and immunotherapeutics

Abstract

Single molecules useful in vaccine compositions, and methods of making and using the same, are described.

What is claimed is: 
     
       1. A composition comprising Formula I: 
       
         
           
           
               
               
           
         
         wherein:
 the dashed line indicates R 3  is optional; 
 Z is —(CH 2 ) 5  or —(CH 2 ) 2 ; 
 R 1  is a heterologous helper T-cell epitope consisting of a sequence of from 7 to 30 amino acids, or a bond; 
 R 2  is a B or T cell epitope consisting of from 7 to 30 amino acids, optionally a TACA incorporated into the peptide sequence; and 
 R 3 , when present, is an O-linked xenoantigen attached to an amino acid either via an alpha or beta linkage; 
 provided, however, that R 1  and R 2  can together be a single epitope selected from (i) a B cell epitope in the form of a carbohydrate antigen derived from bacterial cells, viral envelopes, or other infected cell lines; and (ii) a B or T cell epitope consisting of from 7 to 30 amino acids, optionally including a TACA incorporated into the peptide sequence; 
 
       
       and salts, stereoisomers, racemates, hydrates, and solvates thereof. 
     
     
       2. The composition of  claim 1 , wherein the composition is formulated in liposomes. 
     
     
       3. The composition of  claim 2 , wherein the liposomes comprise 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (DSPE-PEG-MAL). 
     
     
       4. The composition of  claim 2 , wherein the liposomes comprise cholesterol-TEG-Rha, cholesterol, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). 
     
     
       5. The composition of  claim 2 , wherein the liposomes are conjugated to an antibody. 
     
     
       6. The composition of  claim 5 , wherein the antibody comprises anti-mouse F4/80. 
     
     
       7. The composition of  claim 1 , wherein the T-cell epitope is selected from the group consisting of: QYIKANSKFIGITEL (SEQ ID NO: 1); KLFAVWKITYKDTG (SEQ ID NO: 2); YAFKYARHANVGRNAFELFL (SEQ ID NO: 3); ISQAVHAAHAEINEAGR (SEQ ID NO: 4); and A′ KZVAAWTLKAA′ (SEQ ID NO: 5), wherein A′ is D-alanine, and Z is L-cyclohexylalanine. 
     
     
       8. The composition of  claim 1 , wherein R 2  comprises an antigen-amino acid construct selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
       9. The composition of  claim 1 , wherein R 1  and R 2  are together an epitope comprising a tumor glycopeptide sequence having an incorporated TACA, selected from the group consisting of: 
       
         
           
           
               
               
           
         
         and wherein no R 3  group is present. 
       
     
     
       10. The composition of  claim 1 , wherein R 1  and R 2  together are a T-cell epitope comprising a pathogenic or altered diabetic peptide sequence selected from the group consisting of: GTTMVSYQPLGDKV (SEQ ID NO: 6), SYQPLGDKV (SEQ ID NO: 7), SYQPLGDAV (SEQ ID NO: 8), GTTMVSYQPLGDAV (SEQ ID NO: 9), SYQPLGDKA (SEQ ID NO: 10), and GTTMVSYQPLGDKA (SEQ ID NO: 11). 
     
     
       11. The composition of  claim 9 , wherein R 3  comprises a xenoantigen attached to either serine (S) or threonine (T). 
     
     
       12. The composition of  claim 9 , wherein R 3  comprises a xenoantigen-amino acid construct selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
       13. The composition of  claim 9 , wherein R 3  comprises a cluster of two or more Rhamnose epitopes. 
     
     
       14. The composition of  claim 9 , wherein R 3  comprises a cluster of three Rhamnose epitopes. 
     
     
       15. The composition of  claim 1 , wherein the composition comprises glycopeptide (11): 
       
         
           
           
               
               
           
         
       
     
     
       16. The composition of  claim 1 , wherein the composition comprises adjuvant pathogenic diabetic peptide conjugate (13): 
       
         
           
           
               
               
           
         
       
     
     
       17. The composition of  claim 1 , wherein the composition comprises adjuvant altered diabetic peptide conjugate (15): 
       
         
           
           
               
               
           
         
       
     
     
       18. The composition of  claim 1 , wherein the composition comprises MUC1 lipoglycopeptide (22): 
       
         
           
           
               
               
           
         
       
     
     
       19. The composition of  claim 1 , wherein the composition comprises pathogenic peptide (30): 
       
         
           
           
               
               
           
         
       
     
     
       20. A vaccine composition comprising:
 a therapeutically effective amount of a composition of  claim 1 ; and 
 a pharmaceutically acceptable carrier, excipient, or diluent.